Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus

Research output: Contribution to journalArticle

Abstract

Diabetes mellitus (DM) reduces lung function and increases the risk of asthma, chronic obstructive pulmonary disease, pneumonia, and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis in diabetes remains unknown. We investigated the effects of hyperglycemia on EMT in the lungs of gerbils with streptozotocin (STZ)-induced diabetes. Diabetic gerbils exhibited a significantly lower volume fraction of the alveolar airspace and significantly higher septal thickness, volume fraction of the alveolar wall, and lung injury scores than did nondiabetic gerbils. The percentage of 8-hydroxy-2′-deoxyguanosine-positive cells and transforming growth factor-β-positive cells was significantly higher, the expression of E-cadherin was significantly lower, and the expression of N-cadherin was significantly higher in diabetic gerbils than in nondiabetic gerbils. These EMT characteristics were associated with a significant increase in α-smooth muscle actin (SMA) expression and collagen deposition in the lungs of diabetic gerbils. The increased α-SMA expression was co-localized with surfactant protein-C in alveolar type II cells in hyperglycemic animals. In conclusion, our study demonstrates that hyperglycemia induces EMT and contributes to lung fibrosis in an experimental DM model.

Original languageEnglish
Pages (from-to)525-533
Number of pages9
JournalActa Histochemica
Volume120
Issue number6
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Experimental Diabetes Mellitus
Gerbillinae
Hyperglycemia
Lung
Pulmonary Fibrosis
Cadherins
Smooth Muscle
Actins
Alveolar Epithelial Cells
Lung Injury
Transforming Growth Factors
Protein C
Surface-Active Agents
Chronic Obstructive Pulmonary Disease
Pneumonia
Diabetes Mellitus
Fibrosis
Collagen
Asthma

Keywords

  • Diabetes mellitus
  • E-cadherin
  • Epithelial–mesenchymal transition
  • N-cadherin
  • Transforming growth factor-β
  • α-smooth muscle actin

ASJC Scopus subject areas

  • Histology
  • Cell Biology

Cite this

@article{65ee77066a37497d919bf5cc32f5cc05,
title = "Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus",
abstract = "Diabetes mellitus (DM) reduces lung function and increases the risk of asthma, chronic obstructive pulmonary disease, pneumonia, and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis in diabetes remains unknown. We investigated the effects of hyperglycemia on EMT in the lungs of gerbils with streptozotocin (STZ)-induced diabetes. Diabetic gerbils exhibited a significantly lower volume fraction of the alveolar airspace and significantly higher septal thickness, volume fraction of the alveolar wall, and lung injury scores than did nondiabetic gerbils. The percentage of 8-hydroxy-2′-deoxyguanosine-positive cells and transforming growth factor-β-positive cells was significantly higher, the expression of E-cadherin was significantly lower, and the expression of N-cadherin was significantly higher in diabetic gerbils than in nondiabetic gerbils. These EMT characteristics were associated with a significant increase in α-smooth muscle actin (SMA) expression and collagen deposition in the lungs of diabetic gerbils. The increased α-SMA expression was co-localized with surfactant protein-C in alveolar type II cells in hyperglycemic animals. In conclusion, our study demonstrates that hyperglycemia induces EMT and contributes to lung fibrosis in an experimental DM model.",
keywords = "Diabetes mellitus, E-cadherin, Epithelial–mesenchymal transition, N-cadherin, Transforming growth factor-β, α-smooth muscle actin",
author = "Chen, {Chung Ming} and Juan, {Shu Hui} and Pai, {Man Hui} and Chou, {Hsiu Chu}",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.acthis.2018.06.004",
language = "English",
volume = "120",
pages = "525--533",
journal = "Acta Histochemica",
issn = "0065-1281",
publisher = "Urban und Fischer Verlag Jena",
number = "6",

}

TY - JOUR

T1 - Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus

AU - Chen, Chung Ming

AU - Juan, Shu Hui

AU - Pai, Man Hui

AU - Chou, Hsiu Chu

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Diabetes mellitus (DM) reduces lung function and increases the risk of asthma, chronic obstructive pulmonary disease, pneumonia, and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis in diabetes remains unknown. We investigated the effects of hyperglycemia on EMT in the lungs of gerbils with streptozotocin (STZ)-induced diabetes. Diabetic gerbils exhibited a significantly lower volume fraction of the alveolar airspace and significantly higher septal thickness, volume fraction of the alveolar wall, and lung injury scores than did nondiabetic gerbils. The percentage of 8-hydroxy-2′-deoxyguanosine-positive cells and transforming growth factor-β-positive cells was significantly higher, the expression of E-cadherin was significantly lower, and the expression of N-cadherin was significantly higher in diabetic gerbils than in nondiabetic gerbils. These EMT characteristics were associated with a significant increase in α-smooth muscle actin (SMA) expression and collagen deposition in the lungs of diabetic gerbils. The increased α-SMA expression was co-localized with surfactant protein-C in alveolar type II cells in hyperglycemic animals. In conclusion, our study demonstrates that hyperglycemia induces EMT and contributes to lung fibrosis in an experimental DM model.

AB - Diabetes mellitus (DM) reduces lung function and increases the risk of asthma, chronic obstructive pulmonary disease, pneumonia, and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis in diabetes remains unknown. We investigated the effects of hyperglycemia on EMT in the lungs of gerbils with streptozotocin (STZ)-induced diabetes. Diabetic gerbils exhibited a significantly lower volume fraction of the alveolar airspace and significantly higher septal thickness, volume fraction of the alveolar wall, and lung injury scores than did nondiabetic gerbils. The percentage of 8-hydroxy-2′-deoxyguanosine-positive cells and transforming growth factor-β-positive cells was significantly higher, the expression of E-cadherin was significantly lower, and the expression of N-cadherin was significantly higher in diabetic gerbils than in nondiabetic gerbils. These EMT characteristics were associated with a significant increase in α-smooth muscle actin (SMA) expression and collagen deposition in the lungs of diabetic gerbils. The increased α-SMA expression was co-localized with surfactant protein-C in alveolar type II cells in hyperglycemic animals. In conclusion, our study demonstrates that hyperglycemia induces EMT and contributes to lung fibrosis in an experimental DM model.

KW - Diabetes mellitus

KW - E-cadherin

KW - Epithelial–mesenchymal transition

KW - N-cadherin

KW - Transforming growth factor-β

KW - α-smooth muscle actin

UR - http://www.scopus.com/inward/record.url?scp=85048704282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048704282&partnerID=8YFLogxK

U2 - 10.1016/j.acthis.2018.06.004

DO - 10.1016/j.acthis.2018.06.004

M3 - Article

AN - SCOPUS:85048704282

VL - 120

SP - 525

EP - 533

JO - Acta Histochemica

JF - Acta Histochemica

SN - 0065-1281

IS - 6

ER -